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• W2509015198 abstract "Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5′-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N′-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5′-deoxy-5′-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5′-deoxy-5′-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5′-deoxy-5′-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents." @default.
• W2509015198 created "2016-09-16" @default.
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• W2509015198 date "2016-11-01" @default.
• W2509015198 modified "2023-09-30" @default.
• W2509015198 title "Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation" @default.
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• W2509015198 cites W1965713411 @default.
• W2509015198 cites W1968919723 @default.
• W2509015198 cites W1970219648 @default.
• W2509015198 cites W1970403529 @default.
• W2509015198 cites W1975293246 @default.
• W2509015198 cites W1985516715 @default.
• W2509015198 cites W1992834280 @default.
• W2509015198 cites W1994713811 @default.
• W2509015198 cites W1998755101 @default.
• W2509015198 cites W1999776725 @default.
• W2509015198 cites W2000083176 @default.
• W2509015198 cites W2000663742 @default.
• W2509015198 cites W2007742570 @default.
• W2509015198 cites W2018028519 @default.
• W2509015198 cites W2019250374 @default.
• W2509015198 cites W2027482274 @default.
• W2509015198 cites W2037313242 @default.
• W2509015198 cites W2037326045 @default.
• W2509015198 cites W2040130048 @default.
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• W2509015198 cites W2050172943 @default.
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• W2509015198 cites W2065251402 @default.
• W2509015198 cites W2065539299 @default.
• W2509015198 cites W2066018734 @default.
• W2509015198 cites W2069060832 @default.
• W2509015198 cites W2071451059 @default.
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• W2509015198 cites W2090431249 @default.
• W2509015198 cites W2094546717 @default.
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• W2509015198 doi "https://doi.org/10.1016/j.ejmech.2016.08.047" @default.
• W2509015198 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5111791" @default.
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